Sprague-Dawley rats treated with a thiamine deficient diet develop a syndrome that behaviorally and neuropathologically resembles Wernicke's encephalopathy (the acute phase of Korsakoff's psychosis). Preterminal rats (approximately 50% weight of control animals) improve behaviorally within hours after intraperitoneal injection of thiamine and after 2-3 months weigh the same and appear no different from control animals. Recovered animals of both sexes (at least 6 months post-thiamine deficiency) are significantly less sensitive to the effects of alcohol as measured by behavioral impairment and hypothermia perhaps due to increased alcohol metabolism and reduced CNS sensitivity. Therefore, thiamine deficiency may contribute to both the pharmacokinetic and pharmacodynamic tolerance to alcohol observed in chronic alcoholics. The duration of thiamine deficiency required to reach the preterminal state varies greatly and we are in the process of determining which inbred strains are most sensitive to thiamine deficiency and whether this is related to their metabolism of thiamine.